This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To assess neuroprotective strategies for Parkinson's disease using gene therapy to deliver the trophic factor GDNF or the antiapoptotic molecule Bcl-2. Aging and environmental toxins have been identified as risk factors for Parkinson's disease. In order to assess the potential for functional recovery induced by GDNF of a diseased aged primate brain, old male rhesus monkeys presenting a parkinsonian syndrome received intracerebral injections of lentiviral vectors encoding for GDNF or a control treatment. Our results using behavioral tests, imaging and postmortem brain analysis indicate that the aged primate brain exposed to a neurotoxic insult is responsive to GDNF trophic stimulation locally delivered by lentiviral vectors. The value of this research is directly applied to clinical trials to prevent progression of Parkinsonism in patients and this work also provides data on the safety of the method of delivery using lentiviral vectors. This research used Animal Services, CPI, and Pathology Services. PUBLICATION: Emborg M.E. , Moirano J., Zufferey R., Peng S., Ebert A., Joers V., B. Roitberg E., Holden J., Koprich J., Lipton J., Kordower J.H., Aebischer P. (2009) Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF. Neurobiol Dis. 36: 303-311.